Supplementary Material for: A Common Genetic Variant in the Insulin Receptor Gene Is Associated with Eating Difficulties at 2 Years of Age in a Cohort of Preterm Infants

Background/Aims: Children born preterm are more likely than full-term infants to develop eating difficulties that can affect their growth. Although this behavior is certainly influenced by their fetal and postnatal history, a large individual variability exists that results from a complex interaction between genetic and environmental factors. We performed an original pilot study to identify common genetic variants associated with eating difficulties at 2 years of age in the POLYNUCA cohort of preterm infants. Methods: Eating behavior was assessed using a parental questionnaire in a cohort of 234 very preterm infants (including 38 pairs of twins). Eighty-two common single nucleotide polymorphisms (SNPs) were selected in a total of 40 candidate genes involved in the regulation of energy homeostasis and food intake. Results: Eating behavior was strongly correlated in monozygotic (r = 0.92, p = 0.001) but not dizygotic twins (r = 0.27, p = 0.14), suggesting a strong heritability of this trait. One SNP (rs11671975) in the insulin receptor (INSR) gene was significantly associated with eating behavior. This effect was maintained after adjustment for birth weight Z score and maternal education level, two factors that are associated with eating difficulties at 2 years of age. Conclusion: The INSR gene is potentially associated with eating difficulties in preterm infants.